Comparison of defined versus recommended versus prescribed daily doses for measuring hospital antibiotic consumption.

BACKGROUND: Hospital antibiotic use is usually measured by calculating the volume as the number of daily doses defined by the World Health Organization/Anatomical Therapeutic Chemical (WHO/ATC) index (DDDs) divided by a denominator indicating clinical activity, such as the number of occupied bed days. Previous studies have found discrepancies between DDDs, daily doses as recommended in practice guidelines (recommended daily doses, RDDs), and truly prescribed daily doses (PDDs). Very few studies have quantified these discrepancies. METHODS: A point prevalence survey was carried out in defined acute care service areas of a large German state university hospital. Of the 941 adult inpatients present on the day of the survey for whom adequate information was available, 267 (28%) had 471 prescriptions for antimicrobial drugs on that specific day. A check for any additional antimicrobial drug prescriptions for these 267 patients during the six days immediately preceding the survey day yielded a total of 2,304 PDDs, of which 1,754 were antibacterial agents. The latter antibacterial drug PDDs constituted the basis for analysis. The proportion of PDDs different from RDDs and from DDDs was evaluated, and the deviations were calculated. RDD dose definitions corresponded to the local practice guideline recommendations of antibiotic therapy for adult hospitalized patients with normal renal function. RESULTS: Of the 1,754 PDDs, 625 were matching DDD dose definitions (36%), and 1,024 (58%) were matching RDD dose definitions (p < 0.01). Corresponding values for patients with impaired renal function (creatinine clearance < 50 ml/min) were 36% and 42%, respectively. Large DDD discrepancies (< 50% of prescribed doses matching DDD definitions) were noted for beta-lactams and macrolides, while large RDD discrepancies were observed for aminoglycosides. Compared with PDDs, the use of DDDs as the measurement of hospital antibiotic use overestimated antibiotic use volumes by 32%, while the use of RDD led to a slight underestimation (-9%). CONCLUSION: The use of DDDs as currently defined by WHO/ATC for measuring hospital antibiotic consumption may be associated with a substantial overestimation of antibiotic use density, while using practice guideline-derived RDDs may yield more valid antibiotic exposure estimates that would be helpful in cross-sectional and longitudinal analyses of antibiotic consumption.

Ultrasound-guided strategy for provisional stenting with focal balloon combination catheter: results from the randomized Strategy for Intracoronary Ultrasound-guided PTCA and Stenting (SIPS) trial.

BACKGROUND: Intracoronary ultrasound (ICUS) has provided insights into vascular pathology and interventional therapy. The Strategy for ICUS-Guided PTCA and Stenting (SIPS) trial tested the hypothesis that routine ICUS guidance of coronary interventions improves outcome. METHODS AND RESULTS: A single-center consecutive-patient randomized design (with 6-month angiographic and 2-year clinical follow-up) was used. Consecutive patients (no chronic total occlusions or emergency procedures) were randomized to ICUS-guided provisional stenting or standard angiographic guidance. Quantitative angiographic minimal lumen diameter (MLD), angiographic restenosis, clinically driven target lesion revascularization, and major adverse cardiac events (MACEs) were evaluated. A total of 291 procedures (356 lesions) were included. Procedure success was higher in the ICUS-guided group than the group randomized to standard guidance (94. 7% versus 87.4%, respectively; P:=0.033), whereas time (65.2+/-31.0 versus 60.5+/-34.0 minutes, P:=0.18) and contrast use (209.3+/-94.1 versus 197.5+/-89.5 mL, P:=0.23) were not significantly different. Stenting rates were similar (49.7% versus 49.5%, P:=0.89). Acute gain was greater in the ICUS-guided group than in the standard guidance group (1.85+/-0.72 versus 1.67+/-0.76 mm, respectively; P:=0.02). Angiographic 6-month analysis revealed no difference in MLD (1.71+/-0.94 versus 1.57+/-0.90, P:=0.19) or binary restenosis rate (>50% diameter stenosis) (29% versus 35%, P:=0.42). Clinical follow-up (602+/-307 days) showed a significant decrease in clinically driven target lesion revascularization in the ICUS group compared with the standard guidance group (17% versus 29%, respectively; P:=0.02). CONCLUSIONS: Although angiographic MLD did not differ significantly after 6 months, ICUS-guided provisional stenting improved 2-year clinical results after intervention.

[Lipid intervention and coronary heart disease in men less than 56 years of age. The Coronary Intervention Study: CIS]. / Lipid-Intervention und koronare Herzkrankheit bei Männern unter 56 Jahren. Die Coronare Interventions-Studie: CIS.

UNLABELLED: The CIS was undertaken with the aim to evaluate the effects of lipid modifications on angiographic progression and regression of CAD in patients with CAD and hypercholesterolemia. The design included a multicenter randomized, double-blind, parallel, placebo-controlled comparison, with target and safety limits for adjusting the trial medication depending on the LDL cholesterol level (LDL-C) achieved, i.e., up to 40 mg of simvastatin (S) or placebo (P) daily, add-on medication (up to 3 x 4 g Colestyramin), and diet counselling. Male patients, average age 49 (< or = 56) years, were included with angiographic CAD and a screening total cholesterol of 207-350 mg/dl, who were not due to undergo coronary bypass surgery or PTCA, who did not suffer from serious other disease (e.g., diabetes mellitus), and who had not undergone coronary bypass surgery previously. RESULTS: All baseline variables were comparable in the treatment groups, with 129 patients taking S and 125 taking P. Of these 254 patients 217 had their final study visit and 207 underwent a second angiography after an average treatment time of 2.3 years under an average daily dose of 37 mg S. 205 pairs of films were available for analysis. Vital information was obtained of all patients until closure of the data bank, half a year after the last study angiography. Five deaths occurred within the study period, 12 through March 15, 1995 (S: 1/6, P: 4/6). 37 patients (S: 18, P: 19) discontinued trial drug and protocol. Concomitant CAD medication was comparable in both groups, except lipid-lowering add-on medication which was significantly higher in the P group (38% versus 13%). Significant changes in lipid levels, on treatment, were observed in the S group amounting to a mean difference in LDL-C of -35%, in Apo-Protein B (ApoB) of -30%, in VLDL-C of -37%, and in triglycerides (TG) of -27%, and in HDL-C of +6%, in comparison to the control group; these differences were even greater in 137 fully compliant patients: -41, -36, -39, -31, and +7%, respectively. Progression in the S group was significantly less, as defined by the two primary target criteria: 1) the minimum obstruction diameter (MOD), determined by quantitative coronary angiography (QCA), decreased about five times less in comparison to the control group (S: by -0.017; P: -0.0954 mm), and 2) the standardized visual global change score (GCS) deteriorated almost three times less in the S group (by +0.20) than in the P group (+0.58). Of the secondary target criteria, the mean lumen diameter (QCA) also developed a significant difference (S: -0.20; P: +0.23 mm; p = 0.0006) with a trend toward regression in the S group. The QCA-%-stenosis deteriorated three- to four-times less in the S group as compared to the control group (S: by 0.69%; P: by 2.73%; p = 0.0022), and the number of patients with angiographic progression was nearly halved (S: 30%; P: 56%; p < 0.0000). These differences were determined by intention to treat analysis (ITT), and they were obtained in spite of lipid lowering add-on medication in 38% of the P patients; they turned out to be more pronounced in 137 fully compliant patients, in an analysis "as treated". The mean decrease in LDL-C serum level caused by S was significantly correlated to the decrease in progression, and multivariate regression analysis of both treatment groups identified LDL-C (or ApoB) and TG as independent predictors of progression. Progression appeared to be most pronounced in low and medium sized lesions, and the beneficial effect of lipid intervention dominated in lesions with 12-56% QCA stenosis severity. A small fraction of patients who suffered from exercise-induced angina, with ST-segment-depression at the beginning of the study, experienced a significant improvement under S as compared to P treatment. Although the study was not designed to show differences in clinical events, the combined number of all major cardiovascular events tended to be less frequent in the S than in the C gr

The effect of simvastatin on progression of coronary artery disease. The Multicenter coronary Intervention Study (CIS).

BACKGROUND: In several angiographic trials, HMG-CoA reductase inhibitors have shown a beneficial effect on the progression of coronary artery disease. Using 20 mg simvastatin, day-1, a treatment period of up to 4 years was necessary to show a significant reduction in coronary artery disease progression. The question remains however whether higher dosages of simvastatin would be more advantageous in respect to the magnitude of the effect and the required time interval to demonstrate treatment efficacy. METHODS AND RESULTS: In the Coronary Intervention Study (CIS), a multicentre randomized double-blind placebo-controlled study, the effects of lipid-lowering therapy with simvastatin on progression of coronary artery disease in 254 men with documented coronary artery disease and hypercholesterolaemia were investigated. Following a period of lipid-lowering diet, treatment with 40 mg simvastatin or placebo was maintained for an average of 2.3 years. Two primary angiographic endpoints were chosen: the global change score (visual evaluation according to the method of Blankenhorn) and the per patient mean change of minimum lumen diameter (evaluated by the CAAS I system). The mean simvastatin dose was 34.5 mg day-1. In the placebo group, the serum lipids remained unchanged; in comparison to the placebo group the simvastatin group showed a 35% LDL-cholesterol decrease. Coronary angiography was repeated in 205 patients (81%) and 203 film pairs (80%,) were evaluable by quantitative coronary angiography. In the simvastatin and placebo groups, the mean global change scores were +0.20 and +0.58 respectively, demonstrating a significantly slower progression of coronary artery disease in the treatment group (P = 0.02). The change in minimum lumen diameter assessed by computer-assisted quantitative evaluation with the CAAS I system was -0.02 mm in the simvastatin group and -0.10 mm in the placebo group (P = 0.002). In the simvastatin group, there was a significant correlation between the LDL cholesterol levels achieved therapeutically and the per patient mean loss of minimum lumen diameter (r = 0.29; P = 0.003). During the study period, there was no significant difference in the incidence of serious cardiac events (15 of 129 patients in the simvastatin group and 19 of 125 patients in the placebo group, ns). CONCLUSION: Treatment with 40 mg simvastatin day-1 reduces serum cholesterol and slows the progression of coronary artery disease significantly within a short period of treatment time. In the treatment group, retardation of progression is inversely correlated to the LDL-cholesterol levels achieved.

Hemodynamics and exercise tolerance after bisoprolol, nifedipine, and their combination in patients with angina pectoris.

The different mechanisms of action of beta-blockers and calcium antagonists could result in an additive therapeutic effect in patients with angina pectoris. Twenty-one male patients aged between 41 and 68 years and suffering from chronic stable angina pectoris and coronary artery disease confirmed by angiography took part in a randomized, double-blind study to examine the acute effect of 10 mg of bisoprolol, 20 mg of nifedipine, and a combination of the two drugs on hemodynamics at rest and during exercise [heart rate (HR), systolic blood pressure (SBP), rate-pressure product (RPP), cardiac index (CI), total peripheral resistance (TPR), and pulmonary capillary wedge pressure (PCP)], the behavior of the ST segment (ST), and exercise tolerance until occurrence of an ST-segment depression of 0.1 mV (W-ST01) and until onset of anginal pain (W-AP1). Following a baseline exercise test, 11 patients were given 10 mg of bisoprolol orally, whereas 10 patients received placebo. Two hours later, a second exercise test was carried out. All patients in both groups then received 20 mg of N orally. A third exercise test was performed 2 h later. On exercise, bisoprolol resulted in significant changes in HR (-16%), RPP (-22%), and CI (-16%), as well as in TPR (+ 13%); PCP was not significantly affected. Nifedipine led to significant changes in CI (+9%) and PCP (-34%). The effects of bisoprolol on HR and RPP and of nifedipine on PCP were retained in the combination. Competition was detectable as regards the opposing effects on CI and TPR. Measured by W-ST01 and ST, bisoprolol had a marked anti-ischemic effect, whereas that of nifedipine was distinctly less. There was an increase in effect after combination of the drugs (not significant). In patients with chronic angina pectoris due to coronary artery disease, bisoprolol and nifedipine had different hemodynamic profiles after acute administration; when the two drugs were combined, these effects were partly intensified and partly canceled out. There was a tendency for the effect of bisoprolol to be intensified by nifedipine in the combination. The combination of bisoprolol and nifedipine was well tolerated in the doses selected.